lecture 5 somatic nervous system somatic nervous system muscle

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  • The Cyprus International Institute for the Environment and Public HealthIn collaboration with the Harvard School of Public Health

    Constantinos Pitris, MD, PhD

    Assistant Professor, University of Cypruscpitris@ucy.ac.cy

    http://www.eng.ucy.ac.cy/cpitris/courses/CIIPhys/

    Lecture 5

    Neuromuscular Physiology(240-249, 253-267,270-286,288-297)

    Excluded: muscle length, tension, contraction and velocity, phosphorylation of myosin

    2

    Somatic Nervous System

    Consists of axons of motor neurons Originate in spinal cord or brain stem and

    end on skeletal muscle Motor neuron releases neurotransmitter,

    ACh Stimulates muscle contraction

    Motor neurons = final common pathway Various regions of CNS exert control over

    skeletal muscle activity Spinal cord, motor regions of cortex, basal

    nuclei, cerebellum, and brain stem Pathologies

    Polio virus destroys the cell bodies of motor neurons

    Amyotrophic Lateral Sclerosis (ALS) A.k.a. Lou Gehrigs Disease Most common motor neuron disease Gradual degeneration of motor neurons Unknown cause

    3

    Somatic Nervous System

    4

    Muscle

    Comprises largest group of tissues in body Skeletal (30-40% BW), smooth and cardiac

    (10% BW) Controlled muscle contraction allows

    Purposeful movement of the whole body or parts of the body

    Manipulation of external objects Propulsion of contents through various hollow

    internal organs Emptying of contents of certain organs to

    external environment Three types of muscle

    Skeletal muscle Make up muscular system

    Cardiac muscle Found only in the heart

    Smooth muscle Appears throughout the body systems as

    components of hollow organs and tubes

    Classified in two different ways Striated or unstriated Voluntary or involuntary

    Striatedmuscle

    Unstriatedmuscle

    Skeletalmuscle

    Cardiacmuscle

    Smoothmuscle

    Voluntarymuscle

    Involuntarymuscle

  • 5

    Structure of Skeletal Muscle

    Muscle consists a number of muscle fibers lying parallel to one another and held together by connective tissue

    Single skeletal muscle cell is known as a muscle fiber Multinucleated Large, elongated, and

    cylindrically shaped Fibers usually extend entire

    length of muscle

    MuscleTendon

    Muscle fiber(a singlemuscle cell)

    Connectivetissue

    Muscle fiber Dark A band Light I band

    Myofibril

    6

    Neuromuscular Junction

    Axon terminal of motor neuron forms neuromuscular junction with a single muscle cell Terminal button (of neuron) Motor End Plate (of muscle

    cell)

    7

    Neuromuscular Junction

    Signals are passed between nerve terminal and muscle fiber by means of neurotransmitter ACh

    AP in motor neuron reaches terminal

    Voltage-gated Ca2+ channels open ACh is released by exocytosis ACh diffuses across the space and

    binds to receptor sites on motor end plate of muscle cell membrane

    Binding triggers opening of cationchannels in motor end plate

    Na+ movements (larger than K+movements) depolarize motor end plate, producing end-plate potential

    Local current flow between depolarized end plate and adjacent muscle cell membrane brings adjacent areas to threshold

    Action potential is initiated and propagated throughout muscle fiber

    Myelin sheath

    Axonterminal

    Terminal button

    Vesicle of acetylcholine

    Acetylcholinereceptor site

    Acetycholinesterase

    Voltage-gatedNa+ channel

    Chemically gatedcation channel

    Motor end plate

    Contractile elements within muscle fiber

    Voltage-gatedcalcium channel

    Action potentialpropagationin motor neuron

    Action potentialpropagationin muscle fiber

    8

    Neuromuscular Junction

    Acetylcholinesterase On the chemically-gated cation

    channels of the end plate Inactivates ACh (as ACh

    molecules attaches and detaches from the receptors)

    Ends end-plate potential and the action potential

    Ensures prompt termination of contraction

  • 9

    Neuromuscular Junction

    Neuromuscular junction is vulnerable to chemical agents and diseases Black widow spider venom

    Causes explosive release of ACh Prolonged depolarization keeps Na+ channels at inactive state Respiratory failure from diaphragm paralysis

    Botulism toxin From food infected with Clostridium Botulinum Botulism Blocks release of ACh Respiratory failure from inability to contract diaphragm

    Curare Poisonous arrowheads Binds at ACh receptor sites but has no activity and is not degrated

    Organophosphates Pesticide and military nerve gases Prevent inactivation of Ach by inhibiting AChE Effect similar to Black widow spider venom

    Myasthenia gravis inactivates ACh receptor sites Autoimmune condition (Antibodies against ACh receptors) ACh is degraded before it can act. Antidote is neostigmine (inhibits AChE and prolongs ACh action)

    10

    Cross bridge

    Thick filamentThin filament

    Structure of Skeletal Muscle

    Myofibrils Contractile elements of muscle fiber Viewed microscopically myofibril

    displays alternating dark (the A bands) and light bands (the I bands) giving appearance of striations

    Regular arrangement of thick and thin filaments

    Thick filaments myosin (protein) Thin filaments actin (protein)

    Sarcomere Functional unit of skeletal muscle Found between two Z lines

    Z lines connect thin filaments of two adjoining sarcomeres

    Z line A band I band

    Portionof myofibril

    M lineSarcomere

    H zone

    Thick filamentThin filament

    Crossbridges

    M line H zone Z line

    A band I band

    Thick filament Thin filamentMyosin Actin

    11

    Structure of Skeletal Muscle

    Titin Giant, highly elastic protein Largest protein in body Extends in both directions from

    along length of thick filament to Z lines at opposite ends of sarcomere

    Two important roles: Helps stabilize position of thick

    filaments in relation to thin filaments

    Greatly augments muscles elasticity by acting like a spring

    Cross bridge

    Thick filamentThin filament

    Z line A band I band

    Portionof myofibril

    M lineSarcomere

    H zone

    Thick filamentThin filament

    Crossbridges

    M line H zone Z line

    A band I band

    Thick filament Thin filamentMyosin Actin

    12

    Myosin

    Component of thick filament Several hundred of them

    Protein molecule consisting of two identical subunits shaped somewhat like a golf club

    Tail ends are intertwined around each other

    Globular heads project out at one end

    Tails oriented toward center of filament and globular heads protrude outward at regular intervals

    Heads form cross bridges between thick and thin filaments

    Cross bridge has two important sites critical to contractile process

    An actin-binding site A myosin ATPase (ATP-splitting)

    site

    Actin binding siteMyosin ATPase site

    HeadsTail

    Myosin molecule

    Myosin molecule

    Cross bridge

    Thick filament

  • 13

    Actin molecules

    Binding site for attachment with myosin cross bridge

    Actin helix

    +

    Tropomyosin Troponin

    Thin filament

    Actin

    Primary structural component of thin filaments

    Spherical in shape Thin filament also has two other

    proteins Tropomyosin and troponin

    Each actin molecule has special binding site for attachment with myosin cross bridge

    Binding results in contraction of muscle fiber

    Actin and myosin are often called contractile proteins. Neither actually contracts.

    Actin and myosin are not unique to muscle cells, but are more abundant and more highly organized in muscle cells.

    14

    Actin molecules

    Binding site for attachment with myosin cross bridge

    Actin helix

    +

    Tropomyosin Troponin

    Thin filament

    Tropomyosin and Troponin

    Often called regulatory proteins

    Tropomyosin Thread-like molecules that lie

    end to end alongside groove of actin spiral

    In this position, covers actinsites blocking interaction that leads to muscle contraction

    Troponin Made of three polypeptide units

    One binds to tropomyosin One binds to actin One can bind with Ca2+

    15

    Tropomyosin and Troponin

    Troponin When not bound to Ca2+,

    troponin stabilizes tropomyosinin blocking position over actinscross-bridge binding sites

    When Ca2+ binds to troponin, tropomyosin moves away from blocking position

    With tropomyosin out of way, actin and myosin bind, interact at cross-bridges

    Cross-bridge interaction between actin and myosin brings about muscle contraction by means of the sliding filament mechanism

    Thin filament

    TropomyosinCross-bridge binding sites

    Myosin cross bridgeActin binding site

    Relaxed

    Excited

    Actin

    TropomyosinCross-bridge binding site

    Troponin

    16

    Sliding Filament Mechanism

    Thin filaments on each side of sarcomere slide inward

    Over stationary thick filaments Toward center of A band They pull Z lines closer together

    Sarcomere shortens All sarcomeres throughout muscle

    fibers length shorten simultaneously Contraction is accomplished by thin

    filaments from opposite sides of each sarcomere sliding closer together between thick filaments

    Ca2+ plays a key role Increase in Ca2+ starts filament

    sliding Decrease in Ca2+ turns off sliding

    process

    Sarcomere

    Z line H zone I band A band Z line

    Relaxed

    Contracted

    H zoneshorter

    I bandshorter

    A bandsamewidt

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